tbuckley/cabot-search huggingface dataset:
A metabolic role for CD47 in pancreatic β cell insulin secretion and islet transplant outcomes
Authors: Kedar Ghimire, Atharva Kale, Jennifer Li, Sohel M. Julovi, Philip O’Connell, Shane T. Grey, Wayne J. Hawthorne, Jenny E. Gunton, Natasha M. Rogers
Journal: Science Translational Medicine (2023)

Diabetes is a global public health burden and is characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate insulin secretion and improve insulin sensitivity are in high demand as treatment options. CD47 is a cell surface glycoprotein implicated in multiple cellular functions including recognition of self, angiogenesis, and nitric oxide signaling; however, its role in the regulation of insulin secretion remains unknown. Here, we demonstrate that CD47 receptor signaling inhibits insulin release from human as well as mouse pancreatic β cells and that it can be pharmacologically exploited to boost insulin secretion in both models. CD47 depletion stimulated insulin granule exocytosis via activation of the Rho GTPase Cdc42 in β cells and improved glucose clearance and insulin sensitivity in vivo. CD47 blockade enhanced syngeneic islet transplantation efficiency and expedited the return to euglycemia in streptozotocin-induced diabetic mice. Further, anti-CD47 antibody treatment delayed the onset of diabetes in nonobese diabetic (NOD) mice and protected them from overt diabetes. Our findings identify CD47 as a regulator of insulin secretion, and its manipulation in β cells offers a therapeutic opportunity for diabetes and islet transplantation by correcting insulin deficiency.
Carotid Plaque-RADS
Authors: Luca Saba, Riccardo Cau, Alessandro Murgia, Andrew N. Nicolaides, Max Wintermark, Mauricio Castillo, Daniel Staub, Stavros K. Kakkos, Qi Yang, Kosmas I. Paraskevas, Chun Yuan, Myriam Edjlali, Roberto Sanfilippo, Jeroen Hendrikse, Elias Johansson, Mahmud Mossa-Basha, Niranjan Balu, Martin Dichgans, David Saloner, Daniel Bos, H. Rolf Jager, Ross Naylor, Gavino Faa, Jasjit S. Suri, Justin Costello, Dorothee P. Auer, J. Scott Mcnally, Leo H. Bonati, Valentina Nardi, Aad van der Lugt, Maura Griffin, Bruce A. Wasserman, M. Eline Kooi, Jonathan Gillard, Giuseppe Lanzino, Dimitri P. Mikhailidis, Daniel M. Mandell, John C. Benson, Dianne H.K. van Dam-Nolen, Anna Kopczak, Jae W. Song, Ajay Gupta, J. Kevin DeMarco, Seemant Chaturvedi, Renu Virmani, Thomas S. Hatsukami, Martin Brown, Alan R. Moody, Peter Libby, Andreas Schindler, Tobias Saam
Journal: JACC. Cardiovascular imaging (2023)
Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy
Authors: Zheng Cao, Duo Xu, Jeffrey Harding, Wenting Chen, Xiangsheng Liu, Zi Wang, Lan Wang, Tong Qi, Shilin Chen, Xinheng Guo, Irvin S. Y. Chen, Jimin Guo, Yunfeng Lu, Jing Wen
Journal: Science Translational Medicine (2023)

Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity. We report herein a nanocapsule enzyme therapeutic based on lactate oxidase, which reduces lactate concentrations and releases immunostimulatory hydrogen peroxide, averting tumor immunosuppression and improving the efficacy of immune checkpoint blockade treatment. As demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer, this enzyme therapeutic affords an effective tool toward more effective cancer immunotherapy.
Regeneration of neuromuscular synapses after acute and chronic denervation by inhibiting the gerozyme 15-prostaglandin dehydrogenase
Authors: Mohsen A. Bakooshli, Yu Xin Wang, Elena Monti, Shiqi Su, Peggy Kraft, Minas Nalbandian, Ludmila Alexandrova, Joshua R. Wheeler, Hannes Vogel, Helen M. Blau
Journal: Science Translational Medicine (2023)

To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable neuromuscular diseases, or aging. Here, we showed that denervation resulting from transection of the sciatic nerve triggered a marked increase in the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle in mice, providing evidence that injury drives early expression of this aging-associated enzyme or gerozyme. Treating mice with a small-molecule inhibitor of 15-PGDH promoted regeneration of motor axons and formation of neuromuscular synapses leading to an acceleration in recovery of force after an acute nerve crush injury. In aged mice with chronic denervation of muscles, treatment with the 15-PGDH inhibitor increased motor neuron viability and restored neuromuscular junctions and function. These presynaptic changes synergized with previously reported muscle tissue remodeling to result in a marked increase in the strength of aged muscles. We further found that 15-PGDH aggregates defined the target fibers that are histopathologic hallmarks of human neurogenic myopathies, suggesting that the gerozyme may be involved in their etiology. Our data suggest that inhibition of 15-PGDH may constitute a therapeutic strategy to physiologically boost prostaglandin E2, restore neuromuscular connectivity, and promote recovery of strength after acute or chronic denervation due to injury, disease, or aging.
Improved Diagnostic Criteria for Apical Hypertrophic Cardiomyopathy
Authors: Rebecca K. Hughes, Hunain Shiwani, Stefania Rosmini, João B. Augusto, Liam Burke, Yue Jiang, Iain Pierce, George Joy, Silvia Castelletti, Michele Orini, Peter Kellman, Hui Xue, Luis R. Lopes, Saidi Mohiddin, Thomas Treibel, Charlotte Manisty, Gabriella Captur, Rhodri Davies, James C. Moon
Journal: JACC. Cardiovascular imaging (2023)
Clinical Outcomes With a Fully Magnetically Levitated Left Ventricular Assist Device Among Women and Men
Authors: Bhavadharini Ramu, Rebecca Cogswell, Ashwin K. Ravichandran, Joseph Cleveland, Mandeep R. Mehra, Daniel Goldstein, Nir Uriel, Nicholas Dirckx, Sara Ahmed, Melana Yuzefpolskaya
Journal: JACC Heart Failure (2023)
Dasiglucagon Treatment for Postprandial Hypoglycemia After Gastric Bypass: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Casper K. Nielsen, Caroline C. Øhrstrøm, Inas J.K. Houji, Mads M. Helsted, Liva S.L. Krogh, Nicklas J. Johansen, Bolette Hartmann, Jens J. Holst, Tina Vilsbøll, Filip K. Knop
Journal: Diabetes Care (2023)

Postbariatric hypoglycemia affects >50% of individuals who have undergone Roux-en-Y gastric bypass surgery. Despite the often debilitating nature of this complication, existing treatment options are limited and often inefficient. Dasiglucagon is a stable glucagon analog available in a ready-to-use formulation and was recently shown to mitigate postbariatric hypoglycemia in experimental settings. Here, we aimed to evaluate the hypoglycemic hindering potential of dasiglucagon in an outpatient trial.We conducted a randomized, double-blind, placebo-controlled, crossover, proof-of-concept study at the Center for Clinical Metabolic Research at Gentofte Hospital in Denmark. The study included 24 individuals who had undergone Roux-en-Y gastric bypass surgery (n = 23 women) with continuous glucose monitor-verified postbariatric hypoglycemia (≥15 min at <3.9 mmol/L three or more times per week) randomly assigned to two treatment periods of 4 weeks of self-administered subcutaneous dasiglucagon at 120 μg or placebo. The primary and key secondary outcomes were continuous glucose monitor-captured percentage of time in level 1 and 2 hypoglycemia (<3.9 and <3.0 mmol/L), respectively.Compared with placebo, treatment with dasiglucagon significantly reduced time in level 1 hypoglycemia by 33% (-1.2 percentage points; 95% CI -2.0 to -0.5; P = 0.002) and time in level 2 hypoglycemia by 54% (-0.4 percentage points; 95% CI -0.6 to -0.2; P < 0.0001). Furthermore, dasiglucagon corrected hypoglycemia within 15 min in 401 of 412 self-administrations, compared with 104 of 357 placebo self-administrations (97.3% vs. 29.1% correction of hypoglycemia rate; P < 0.001). Dasiglucagon was generally well tolerated, with mostly mild to moderate adverse events of nausea.Compared with placebo, 4 weeks of self-administered dasiglucagon effectively reduced clinically relevant hypoglycemia in individuals who had undergone Roux-en-Y gastric bypass surgery.
A Phase I Expansion Cohort Study Evaluating the Safety and Efficacy of the CHK1 Inhibitor LY2880070 with Low-dose Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
Authors: Brandon M. Huffman, Hanrong Feng, Kalindi Parmar, Junning Wang, Kevin S. Kapner, Bose Kochupurakkal, David B. Martignetti, Golbahar Sadatrezaei, Thomas A. Abrams, Leah H. Biller, Marios Giannakis, Kimmie Ng, Anuj K. Patel, Kimberly J. Perez, Harshabad Singh, Douglas A. Rubinson, Benjamin L. Schlechter, Elizabeth Andrews, Alison M. Hannigan, Stanley Dunwell, Zoe Getchell, Srivatsan Raghavan, Brian M. Wolpin, Caroline Fortier, Alan D. D'Andrea, Andrew J. Aguirre, Geoffrey I. Shapiro, James M. Cleary
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Combining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine combined with the CHK1 inhibitor LY2880070 in patients with previously treated advanced PDAC. Patients and Methods: Patients with metastatic PDAC were treated with gemcitabine intravenously at 100 mg/m2 on days 1, 8, and 15, and LY2880070 50 mg orally twice daily on days 2–6, 9–13, and 16–20 of each 21-day cycle. Pretreatment tumor biopsies were obtained from each patient for correlative studies and generation of organoid cultures for drug sensitivity testing and biomarker analyses. Results: Eleven patients with PDAC were enrolled in the expansion cohort between August 27, 2020 and July 30, 2021. Four patients (36%) experienced drug-related grade 3 adverse events. No objective radiologic responses were observed, and all patients discontinued the trial by 3.2 months. In contrast to the lack of efficacy observed in patients, organoid cultures derived from biopsies procured from two patients demonstrated strong sensitivity to the gemcitabine/LY2880070 combination and showed treatment-induced upregulation of replication stress and DNA damage biomarkers, including pKAP1, pRPA32, and γH2AX, as well as induction of replication fork instability. Conclusions: No evidence of clinical activity was observed for combined low-dose gemcitabine and LY2880070 in this treatment-refractory PDAC cohort. However, the gemcitabine/LY2880070 combination showed in vitro efficacy, suggesting that drug sensitivity for this combination in organoid cultures may not predict clinical benefit in patients.
Phase II Trial of Nivolumab in Metastatic Rare Cancer with dMMR or MSI-H and Relation with Immune Phenotypic Analysis (the ROCK Trial)
Authors: Hitomi S. Okuma, Keisuke Watanabe, Kenji Tsuchihashi, Ryunosuke Machida, Ryo Sadachi, Akihiro Hirakawa, Hiroshi Ariyama, Masashi Kanai, Masahisa Kamikura, Kenta Anjo, Akari Hiramitsu, Shigeki Sekine, Natsuko Okita, Hiroyuki Mano, Hiroyoshi Nishikawa, Kenichi Nakamura, Kan Yonemori
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) are positive predictive markers for immune checkpoint inhibitors. However, data on the activity of nivolumab in advanced dMMR/MSI-H rare cancers and more accurate biomarkers are worth exploring. Patients and Methods: We conducted a multicenter phase II, open-label, single-arm clinical trial to explore the effectiveness and safety of nivolumab monotherapy in patients with advanced rare cancers with dMMR/MSI-H, in parallel with immune phenotype analysis, to explore new biomarkers. A Bayesian adaptive design was applied. Characterization of peripheral blood mononuclear cells (PBMC) was characterized by multicolor flow cytometric analysis and CyTOF using samples collected before and after the intervention. The dMMR was identified by the complete loss of MLH1/MSH2/MSH6/PMS2. Results: From May 2018 to March 2021, 242 patients were screened, and 11 patients were enrolled, of whom 10 were included in the full analysis. Median follow-up was 24.7 months (interquartile range, 12.4–31.5). Objective response rate was 60% [95% confidence interval (CI), 26.2–87.8] by central assessment and 70% (95% CI, 34.8–93.3) by local investigators. Median progression-free survival was 10.1 months (95% CI, 0.9–11.1). No treatment-related adverse events of grade 3 or higher were observed. Patients with a tumor mutation burden of ≥10/Mb showed a 100% response rate (95% CI, 47.8–100). Responders had increased T-bet+ PD-1+ CD4+ T cells in PBMC compared with nonresponders (P &amp;lt; 0.05). Conclusions: The trial met its primary endpoint with nivolumab, demonstrating clinical benefit in advanced dMMR/MSI-H rare solid cancers. Besides, the proportion of T-bet+ PD-1+ CD4+ T-cells may serve as a novel predictive biomarker.
FAK Drives Resistance to Therapy in HPV-Negative Head and Neck Cancer in a p53-Dependent Manner
Authors: Phillip M. Pifer, Liangpeng Yang, Manish Kumar, Tongxin Xie, Mitchell Frederick, Andrew Hefner, Beth Beadle, David Molkentine, Jessica Molkentine, Annika Dhawan, Mohamed Abdelhakiem, Abdullah A. Osman, Brian J. Leibowitz, Jeffrey N. Myers, Curtis R. Pickering, Vlad C. Sandulache, John Heymach, Heath D. Skinner
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Radiation and platinum-based chemotherapy form the backbone of therapy in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). We have correlated focal adhesion kinase (FAK/PTK2) expression with radioresistance and worse outcomes in these patients. However, the importance of FAK in driving radioresistance and its effects on chemoresistance in these patients remains unclear. Experimental Design: We performed an in vivo shRNA screen using targetable libraries to identify novel therapeutic sensitizers for radiation and chemotherapy. Results: We identified FAK as an excellent target for both radio- and chemosensitization. Because TP53 is mutated in over 80% of HPV-negative HNSCC, we hypothesized that mutant TP53 may facilitate FAK-mediated therapy resistance. FAK inhibitor increased sensitivity to radiation, increased DNA damage, and repressed homologous recombination and nonhomologous end joining repair in mutant, but not wild-type, TP53 HPV-negative HNSCC cell lines. The mutant TP53 cisplatin-resistant cell line had increased FAK phosphorylation compared with wild-type, and FAK inhibition partially reversed cisplatin resistance. To validate these findings, we utilized an HNSCC cohort to show that FAK copy number and gene expression were associated with worse disease-free survival in mutant TP53, but not wild-type TP53, HPV-negative HNSCC tumors. Conclusions: FAK may represent a targetable therapeutic sensitizer linked to a known genomic marker of resistance.
Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma
Authors: Tiansuo Zhao, Tingting Jiang, Xiaojia Li, Shaofei Chang, Qihui Sun, Fanyang Kong, Xiangyu Kong, Fang Wei, Jie He, Jihui Hao, Keping Xie
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains. Experimental Design: Gene expression and its association with clinicopathologic characteristics of patients with PDA and mouse models were analyzed using IHC. Protein expression and their regulation were measured by Western blot and immunoprecipitation analyses. Protein interactions were determined using gain- and loss-of-function assays and molecular methods, including chromatin immunoprecipitation, co-immunoprecipitation, and dual luciferase reporter. Results: There was concomitant overexpression of both GRP78 and HIF-1α in human and mouse PDA tissues and cells. Glucose deprivation increased the expression of GRP78 and HIF-1α, particularly colocalization in nucleus. Induction of HIF-1α expression by glucose deprivation in PDA cells depended on the expression of and its own interaction with GRP78. Mechanistically, increased expression of both HIF-1α and LDHA under glucose deprivation was caused by the direct binding of GRP78 and HIF-1α protein complexes to the promoters of HIF-1α and LDHA genes and transactivation of their transcriptional activity. Conclusions: Protein complex of GRP78 and HIF-1α directly binds to HIF-1α own promoter and LDHA promoter, enhances the transcription of both HIF-1α and LDHA, whereas glucose deprivation increases GRP78 expression and further enhances HIF-1α and LDHA transcription. Therefore, crosstalk and integration of hypoxia- and hypoglycemia-responsive signaling critically impact PDA metabolic reprogramming and therapeutic resistance.
Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC)
Authors: MinKe He, YeXing Huang, ZeFeng Du, ZhiCheng Lai, Hanyue Ouyang, JingXian Shen, DongSheng Wen, QiJiong Li, YaoJun Zhang, Wei Wei, MinShan Chen, Li Xu, Anna Kan, Ming Shi
Journal: Clinical Cancer Research (2023)

To investigate the efficacy, safety, and biomarkers of systemic chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) in combination with lenvatinib and toripalimab as the first-line treatment for advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis.
The Importance of Representation and Gender Valuation in the Field of Neurological Surgery
Authors: Estefania G. Narvaez, Stacey Q. Wolfe, Julie Ann Freischlag
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Intentionality Is Needed to Diversify Surgical Leadership
Authors: M. Libby Weaver, Melina R. Kibbe
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Mesh and Hiatal Hernia Repair—The Never-Ending Saga
Authors: Marco G. Patti, Fernando A. M. Herbella
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Analysis of Social Media Involvement in Violent Injury
Authors: Anna E. Garcia Whitlock, Brendan P. Gill, Joseph B. Richardson, Desmond U. Patton, Bethany Strong, Chidinma C. Nwakanma, Elinore J. Kaufman
Journal: JAMA Surgery (2023)

This cross-sectional study uses police agency–collected information to quantify the association among social media involvement, crime, and violence.
Mitochondrial Respiration and Exercise Performance in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Johannes Burtscher, Martin Burtscher
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal